Modulation of riboflavin biosynthesis and utilization in mycobacteria.

Unlabelled: Riboflavin (vitamin B) is the precursor of the flavin coenzymes, FAD and FMN, which play a central role in cellular redox metabolism. While humans must obtain riboflavin from dietary sources, certain microbes, including (Mtb), can biosynthesize riboflavin . Riboflavin precursors have also been implicated in the activation of mucosal-associated invariant T (MAIT) cells which recognize metabolites derived from the riboflavin biosynthesis pathway complexed to the MHC-I-like molecule, MR1.

Current Perspectives and Challenges of MAIT Cell-Directed Therapy for Tuberculosis Infection.

Mucosal-associated invariant T (MAIT) cells are a distinct population of non-conventional T cells that have been preserved through evolution and possess properties of both innate and adaptive immune cells. They are activated through the recognition of antigens presented by non-polymorphic MR1 proteins or, alternately, can be stimulated by specific cytokines. These cells are multifaceted and exert robust antimicrobial activity against bacterial and viral infections, direct the immune response through the modulation of other immune cells, and exhibit a specialized tissue homeostasis and repair function.

Modulation of riboflavin biosynthesis and utilization in mycobacteria.

Riboflavin (vitamin B) is the precursor of the flavin coenzymes, FAD and FMN, which play a central role in cellular redox metabolism. While humans must obtain riboflavin from dietary sources, certain microbes, including (Mtb), can biosynthesize riboflavin . Riboflavin precursors have also been implicated in the activation of mucosal-associated invariant T (MAIT) cells which recognize metabolites derived from the riboflavin biosynthesis pathway complexed to the MHC-I-like molecule, MR1.

The detection of mixed tuberculosis infections using culture filtrate and resuscitation promoting factor deficient filtrate.

Tuberculosis (TB) infected individuals harbor a heterogenous population of differentially culturable tubercle bacilli (DCTB). Herein, we describe how DCTB assays using culture filtrate either containing or deficient in resuscitation promoting factors can uncover mixed infections. We demonstrate that () strain genotypes can be separated in DCTB assays based on their selective requirement for growth stimulatory factors.

DNA-Dependent Binding of Nargenicin to DnaE1 Inhibits Replication in .

Natural products provide a rich source of potential antimicrobials for treating infectious diseases for which drug resistance has emerged. Foremost among these diseases is tuberculosis. Assessment of the antimycobacterial activity of nargenicin, a natural product that targets the replicative DNA polymerase of , revealed that it is a bactericidal genotoxin that induces a DNA damage response in () and inhibits growth by blocking the replicative DNA polymerase, DnaE1.

Deletion of N-acetylmuramyl-L-alanine amidases alters the host immune response to infection.

Peptidoglycan (PG), a heteropolysaccharide component of the mycobacterial cell wall can be shed during tuberculosis infection with immunomodulatory consequences. As such, changes in PG structure are expected to have important implications on disease progression and host responses during infection with . Mycobacterial amidases have important roles in remodeling of PG during cell division and are implicated in susceptibility to antibiotics.

Biological Profiling Enables Rapid Mechanistic Classification of Phenotypic Screening Hits and Identification of KatG Activation-Dependent Pyridine Carboxamide Prodrugs With Activity Against .

Compounds with novel modes of action are urgently needed to develop effective combination therapies for the treatment of tuberculosis. In this study, a series of compounds was evaluated for activity against replicating and Vero cell line toxicity. Fourteen of the compounds with activities in the low micrometer range and a favorable selectivity index were classified using reporter strains of which showed that six interfered with cell wall metabolism and one disrupted DNA metabolism.

Intervening along the spectrum of tuberculosis: meeting report from the World TB Day nanosymposium in the Institute of Infectious Disease and Molecular Medicine at the University of Cape Town.

Tuberculosis (TB), caused by the highly infectious  , remains a leading cause of death worldwide, with an estimated 1.6 million associated deaths reported in 2017. In South Africa, an estimated 322,000 (range 230,000-428,000) people were infected with TB in 2017, and a quarter of them lost their lives due to the disease.

Resuscitation-Promoting Factors Are Required for Mycobacterium smegmatis Biofilm Formation.

Resuscitation-promoting factors (Rpfs) have previously been shown to act as growth-stimulatory molecules via their lysozyme-like activity on peptidoglycan in the bacterial cell wall. In this study, we investigated the ability of strains lacking genes to form biofilms and tested their susceptibilities to cell wall-targeting agents. contains four distinct homologues, namely, MSMEG_5700 (), MSMEG_5439 (), MSMEG_4640 (), and MSMEG_4643 ().

Detection and Quantification of Differentially Culturable Tubercle Bacteria in Sputum from Patients with Tuberculosis.

Rationale: Recent studies suggest that baseline tuberculous sputum comprises a mixture of routinely culturable and differentially culturable tubercle bacteria (DCTB). The latter seems to be drug tolerant and dependent on resuscitation-promoting factors (Rpfs).

Objectives: To further explore this, we assessed sputum from patients with tuberculosis for DCTB and studied the impact of exogenous culture filtrate (CF) supplementation ex vivo.